Aggressive dose de-escalation of radiotherapy provides similar efficacy and superior safety profile in patients with human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), according to a recent study presented at the 2017 Annual Meeting of the American Society for Radiation Oncology (ASTRO).

The phase II single-arm MC1273 study was performed in 80 postsurgery HPV-positive OPSCC patients from September 2013 to June 2016. The patients were treated with radiotherapy of 30 Gy delivered in 1.5 Gy twice daily over 12 days, along with weekly docetaxel. The therapeutic strategy resulted in a tumour control rate of 95 percent and disease-free survival (DFS) rate of 89 percent. [ASTRO 2017, abstract LBA 14]

The trial also demonstrated a distant control rate of 94 percent, along with improved swallowing function from baseline at 12-month follow up (MBSImP [modified barium swallow impairment profile], 47.4 vs 48.6; p=0.03).

There were no significant declines in other quality of life (QoL) scales, including the FACT H&N (Functional Assessment of Cancer Therapy–Head and Neck Version 4), the EuroQol EQ-5D and the EORTC-HN (European Organisation for Research and Treatment of Cancer instrument for head and neck cancer).

“The profile of the typical oropharyngeal cancer patient has changed, which means that our approach to treating this disease needs to change as well…Our findings indicate that this more aggressive approach of cutting the radiation dose by half can be viable for appropriately selected patients,” said lead investigator Dr Daniel Ma from the Mayo Clinic, Rochester, Minnesota, US.

Patients enrolled in the study had minimal smoking history and a median age of 60.5 years. They had stage III or IV disease and received a 50 percent reduction from the standard dose of 60–66 Gy. [J Clin Oncol 2014;32:2486-2495] Those with extracapsular extension received an additional simultaneous radiation boost with a total dose of 36 Gy in 1.8 Gy twice daily.

Eighteen percent of patients experienced cumulative grade 3 or higher toxicity within 3 months, with complete resolution of symptoms by 6 months after treatment. One patient experienced a temporary grade 4 event related to chemotherapy.

There were no grade 3 or higher toxicity observed at 1 or 2 years after treatment.

“Side effects with dose-reduced radiotherapy were dramatically less than what we usually see in treatment of adjuvant radiation therapy for HPV-positive OPSCC patients. For example, no patient in this trial needed a feeding tube placed, whereas close to a third of patients had feeding tubes placed with traditional doses in other recent clinical trials,” explained Ma.

“Aggressive treatment de-escalation resulted in locoregional control rates comparable to historical controls, with low toxicity and no decrements in swallowing function or QoL,” the authors concluded.

The currently ongoing multicentre phase III DART-HPV trial will confirm the efficacy of this treatment approach. 

The standard treatment for OPSCC can include surgery with radiotherapy and/or chemotherapy, which usually causes life-changing symptoms.